Anterior Hypothalamic Lesions Research Articles

Clinical and Experimental Study on Thermoregulatory System and its Relation with Vasomotor Rhinitis

Introduction
 Much of the perennial cold are of vasomotor origin still a less appreciated phenomenon even among the medical personnel, much of which is dubbed in a cursorily in the clinical analogue of a west paper wrap as ‘allergic rhinitis’. This study was attempted to find out the role of thermoregulatory system with causation of vasomotor rhinitis and assessing role of hypothalamus in causation of vasomotor rhinitis.
 Materials and Methods
 In this study conducted during the period of July 1987 to August 1988, 20 normal adult individuals were taken as control and thermoregulatory study was done on them. The results were compared with cases of vasomotor rhinitis/non-allergic rhinopathy cases. In experimental study thermoregulatory study was done on albino rats before and after stereotaxis of anterior and posterior hypothalamic nuclei and the result were compared before stereotaxis and post stereotaxis.
 Results
 Among human study in clinical subjects, patient suffering from vasomotor rhinitis showed a definite shift towards thermoregulatory imbalance both for generalized body caloric fluctuation and particularly on the nasal mucosa. Post-vidian neurectomy results for thermoregulation test was highly significant. In animal study post-hypothalamic stereotaxis temperature measurement showed minimal depression. Dorsal anterior hypothalamic lesion ablation showed significant derangement in the thermoregulatory tolerance profile of the rats’ belly temperature. Posterior hypothalamic lesion showed that there may be some amount of derangements in the thermoregulatory tolerance, which however is not statistically conclusive. Thermoregulatory control is done at hypothalamus, particularly at anterior hypothalamic nuclei level and posterior hypothalamic nuclei in the brain. Thermoregulatory study proves a close correlation between non allergic rhinitis with imbalance in central thermal regulation by hypothalamus.
 Conclusion
 Thermoregulatory study in control and clinical subjects proves a close correlation between vasomotor rhinitis and sympathetic, parasympathetic system.

Eating behaviour and oxytocin in patients with childhood-onset craniopharyngioma and different grades of hypothalamic involvement.

Patients with childhood-onset craniopharyngioma (CP) often suffer from tumour or treatment-related hypothalamic lesions (HL). These lesions may alter production of oxytocin, which plays a major role in the regulation of eating behaviour and body composition. In CP with different degrees of HL, we investigated associations between HL, eating behaviour/eating attitudes, and oxytocin saliva concentrations (OSC). In a cross-sectional case-control study on 34 CP and 73 healthy controls, OSC were measured before, and 60minutes after breakfast by immunoassay. Eating behaviour, attitudes, and habits were assessed by standardized questionnaires. CP with anterior+posterior HL presented with more adverse eating behaviours/symptoms of eating disorders than CP without HL, CP with anterior HL, and controls. Eating behaviour in CP with anterior HL was similar to controls, except for their tendency towards high dietary restraints. Decreases in postprandial compared with fasting OSC were associated with adverse eating behaviour in CP and controls and with higher BMI in CP. CP with anterior HL and CP with anterior+posterior HL present with distinct patterns of eating behaviour. Reduced postprandial compared with fasting OSC is associated with weight problems in CP and with adverse eating behaviour and symptoms of eating disorders in both CP and controls.

OR16-3 Posterior Hypothalamus-Sparing Surgery Improves Outcome after Childhood Craniopharyngioma: Results of the Prospective Multinational Trial Kraniopharyngeom 2007

Background: Quality of survival (QoS) is frequently impaired in childhood-onset craniopharyngioma (CP) patients by hypothalamic syndrome. The debate, whether pretreatment hypothalamic involvement (HI) has apriori prognostic impact or treatment-related hypothalamic lesions (HL) determine outcome, is controversial. Methods: In cross-sectional prospective study, survival and outcome of 109 CPs recruited 2007-2014 in KRANIOPHARYNGEOM 2007 with reference-confirmed presurgical, anterior and posterior HI were analyzed with regard to surgical HL (no, anterior or anterior and posterior HL). Body mass index (BMI), QoS assessed by PEDQOL, and functional capacity (FMH) were measured at diagnosis, during follow-up, and at last visit (median follow-up: 6 years). Results: Surgical HL were reference-confirmed in 86 of 109 (79%) CP (29 anterior, 57 anterior and posterior HL). PFS and BMI at diagnosis were similar in CP subgroups with different degree of HL. CP with anterior and posterior HL presented with higher BMI at one-year follow-up (median BMI: +5.21 SD) and at last visit (BMI: +5.74 SD), when compared to patients without HL (BMI, one year: +1.72 SD, p=0.001; last visit BMI: +2.27 SD, p<0.001) and when compared to patients with anterior HL (BMI, 1 year: +2.46 SD, p=0.002; last visit: +2.87 SD, p=0.001). QoS improved during follow-up in CP without HL for physical functionality (p=0.047), emotional stability (p=0.040), and social functionality (p=0.002) when compared to CP with anterior and posterior HL. Functional capacity was not associated with degree of HL. Conclusions: Based on appropriate preoperative staging, posterior hypothalamus-sparing surgical strategies do not increase risk for relapse/progression, improve QoS and ameliorate development of obesity in CP at risk for obesity due to presurgical anterior and posterior HI.

Posterior hypothalamus-sparing surgery improves outcome after childhood craniopharyngioma.

ObjectiveQuality of life (QoL) is frequently impaired in childhood-onset craniopharyngioma (CP) by hypothalamic syndrome. The debate, whether pretreatment hypothalamic involvement (HI) has apriori prognostic impact or surgical hypothalamic lesions (HL) determine outcome, is controversial.DesignSurvival and outcome of CPs recruited between 2007 and 2014 in KRANIOPHARYNGEOM 2007 were analyzed with regard to reference-confirmed presurgical HI and surgical HL.MethodsRadiological findings, BMI and QoL were assessed at diagnosis and during follow-up. QoL was assessed using Pediatric Quality of Life (PEDQOL) questionnaire.ResultsOne hundred sixty-nine CPs were included presenting with no HI (n = 11), anterior (n = 49) and anterior + posterior (a + p) HI (n = 109) prior to surgery. The latter 109 were analyzed for postoperative HL (no lesion: n = 23, anterior HL: n = 29, a + pHL: n = 57). Progression-free survival (PFS) was higher after complete resection. The highest PFS was observed in CP with a + pHL, especially when compared between non-irradiated subgroups (P = 0.006). Overall survival (OS) rates were 1.0 in all subgroups. CP with a + pHL developed higher BMI (P ≤ 0.001) during follow-up compared between subgroups. 55/109 pts with a + pHI completed PEDQOL at diagnosis (48/109 at 3 years follow-up). QoL was worse for a + pHL patients in terms of physical, social and emotional functionality when compared with the anterior HL and no HL subgroup. BMI development and QoL during follow-up were similar for patients with anterior HL and without HL.ConclusionsPosterior hypothalamus-sparing surgical strategies are associated with higher QoL, decreased development of obesity and lower PFS in CP.

Tadalafil: Protective Action against the Development of Multiple Organ Failure Syndrome

IntroductionMultiple organ failure syndrome (MOFS) is a pathology associated to unspecified and severe trauma, characterized by elevated morbidity and mortality. The complex inflammatory MOFS-related reactions generate important ischemia-reperfusion responses in the induction of this syndrome. Nitric oxide elevation, through the activation of cyclic guanosine monophosphate (cGMP), has the potential of counteracting the typical systemic vasoconstriction, and platelet-induced hypercoagulation. Tadalafil would possibly act protectively by reducing cGMP degradation with consequent diffuse vasodilatation, besides reduction of platelet-induced hypercoagulation, thus, preventing multiple organ failure syndrome development.MethodsThe experimental protocol was previously approved by an institution animal research committee. Experimental MOFS was induced through the stereotaxic micro-neurosurgical bilateral anterior hypothalamic lesions model. Groups of 10 Wistar rats were divided into:a) Non-operated control;b) Operated control group;c) 2 hours after tadalafil-treated operated group;d) 4 hours after tadalafil-treated operated group;e) 8 hours after post-treated operated group. The animals were sacrificed 24 hours after the neurosurgical procedure and submitted to histopathologic examination of five organs: brain, lungs, stomach, kidneys, and liver.ResultsThe electrolytic hypothalamic lesions resulted in a full picture of MOFS with disseminated multiple-organs lesions, provoked primarily by diffusely spread micro-thrombi. The treatment with tadalafil 2 hours after the micro-neurosurgical lesions reduced the experimental MOFS lesions development, in a highly significant level (P<0.01) of 58.75%. The treatment with tadalafil, 4 hours after the micro-neurosurgically-induced MOFS lesions, also reduced in 49.71%, in a highly significant level (P<0.01). Finally, the treatment with tadalafil 8 hours after the neurosurgical procedure resulted in a statistically significant reduction of 30.50% (P<0.05) of the experimentally-induced MOFS gravity scores.ConclusionThe phosphodiesterase 5 inhibitor, tadalafil, in the doses and timing utilized, showed to protect against the experimentally-induced MOFS.

Persistent estrus rat models of polycystic ovary disease: an update

To critically review published articles on polycystic ovary (PCO) disease in rat models, with a focus on delineating its pathophysiology. Review of the English-language literature published from 1966 to March 2005 was performed through PubMed search. Keywords or phrases used were persistent estrus, chronic anovulation, polycystic ovary, polycystic ovary disease, and polycystic ovary syndrome. Articles were also located via bibliographies of published literature. University Health Sciences Center. Articles on persistent estrus and PCO in rats were selected and reviewed regarding the methods for induction of PCO disease. Changes in the reproductive cycle, ovarian morphology, hormonal parameters, and factors associated with the development of PCO disease in rat models were analyzed. Principal methods for inducing PCO in the rat include exposure to constant light, anterior hypothalamic and amygdaloidal lesions, and the use of androgens, estrogens, antiprogestin, and mifepristone. The validated rat PCO models provide useful information on morphologic and hormonal disturbances in the pathogenesis of chronic anovulation in this condition. These studies have aimed to replicate the morphologic and hormonal characteristics observed in the human PCO syndrome. The implications of these studies to human condition are discussed.

Electroacupuncture Enhancement of Natural Killer Cell Activity Suppressed by Anterior Hypothalamic Lesions in Rats

Background/Objective: Neuroendocrine hormones are derived from the hypothalamus. The central nervous system, particularly the hypothalamus, is capable of modulating the cytolytic activity of adherent natural killer (NK) cells. In addition, electroacupuncture (EA) stimulation of the Zusanli (ST36) acupoint enhances splenic NK cell and cytokine activities in rats. However, it is still unclear whether the anterior hypothalamus affects this immunomodulation. Therefore, the aim of the present study was to examine the effect of EA stimulation at the Zusanli acupoint on the NK cell activity modulated by an anterior hypothalamic area lesion. Methods: Male Sprague-Dawley rats were used. Lesions were placed by means of a direct current through a concentric electrode. The electric acupuncture stimulation was delivered for 30 min per each experiment at the right ST36 acupoint with an electrical stimulator. The NK cell activity of the spleen was measured by a fluorescence assay. Results: The NK cell activity was significantly reduced on the 2nd day after the lesion, but was restored to that of the sham group by the 7th day. However, when EA was applied for 2 days after the operation, the NK cell activity of the lesion group was restored to that of the sham group. After 7 days of EA, the NK cell activity of the lesion group was slightly higher than that of the sham group. Conclusion: From these results, we can suggest that EA enhances or restores the NK cell activity suppressed by an anterior hypothalamic area lesion.

Chapter 4 Neuronal networks controlling thermoregulatory effectors

Publisher Summary This chapter summarizes the present knowledge about neuronal networks controlling thermoregulation, mainly knowledge about the efferent pathways from the hypothalamus. The body temperature of a homeothermic animal is regulated by multiple behavioral and autonomic effector responses, and the thermoreceptors responsible for these responses are distributed throughout the body. They are present in not only the skin and the hypothalamus but also in other brain areas and deep in the bodycore. The rostra1 ventrolateral medulla of a cat contains neurons projecting to the spinal cord and presumably sending signals to the sympathetic. Direct recording of sympathetic nerve activities in humans has revealed that skin sympathetic nerves contain vasoconstrictor and sudomotor fibers and that cutaneous sympathetic nerve activity is not correlated with the changes in blood pressure. Animals with preoptic and anterior hypothalamic lesions thermoregulate behaviorally, as well as control animals do, even though they show severe deficits in autonomic regulation. The only part of the neocortex or limbic system that has been systematically investigated in regard to behavioral thermoregulation is the sulcal prefrontal cortex in the rat.

The Effects of Anterior Hypothalamic Lesions on Short-Day Responses in Siberian Hamsters Given Timed Melatonin Infusions

The suprachiasmatic nucleus (SCN) of the hypothalamus is an area of dense 2-[125I]Iodomelatonin binding in Siberian hamsters (Phodopus sungorus sungorus) that is suggestive of a possible role in the reception and/or relaying of melatonin (MEL) signals. Indeed, in pinealectomized male Siberian hamsters given short day (SD) MEL signals (long-duration MEL infusions), lesions of the SCN (SCNx) block testicular regression and decreases in body and fat pad masses seen in identically treated hamsters with sham lesions (SCNs). In similar studies using Syrian hamsters (Mesocricetus auratus), anterior hypothalamic lesions (AHx), but not SCNx, blocked SD MEL signal-induced gonadal regression despite the similarity in the 2-[125I]Iodomelatonin binding pattern between the two species. The discrepancy between the ability of SCNx to block the reception of SD MEL signals between the two species is puzzling, given the similarity in the reproductive status of the Syrian and Siberian hamsters to systemically administered and timed MEL infusions. One possible way of reconciling the differences between these studies was that ancillary damage to areas neighboring the SCN, including the AH, may have occurred in our attempt to achieve complete SCNx in Siberian hamsters. Therefore, the purpose of the present study was to challenge AHx Siberian hamsters with SD MEL signals. Adult male hamsters were pinealectomized, fitted with subcutaneous catheters, and given daily timed infusions of MEL for 5 or 10 h (long day-like and short day-like, respectively) or the saline vehicle for 6 wk following bilateral electrolytic, or sham (AHs) lesions of the AH. Hamsters receiving 10 h MEL infusions that lacked evidence of anatomical or functional damage to the SCN showed SD-like gonadal regression, decreases in body and fat pad mass, and food intake similar to that observed in AHs animals. In contrast, 10 h MEL-infused SCNx hamsters did not exhibit SD-like responses, a finding confirming our previous report. These data suggest that interspecies differences exist between Syrian and Siberian hamsters in central nervous system sites and pathways involved in the reception/transmission of SD MEL signals.

Effect of anterior hypothalamic area lesions on photoperiod-induced shifts in reproductive activity of the ewe

The areas of the brain involved in photoperiodic control of reproduction are not well defined. The objective of this study was to determine whether anterior hypothalamic area (AHA) lesions in the ewe affected the responses of the reproductive system to shifts in the length of the daily photoperiod and development of photorefractoriness to a constant short day photoperiod. Eleven intact ewes received bilateral radiofrequency lesions of the AHA (AHAX), and five received sham lesions (sham). The ewes then were placed in photochambers and exposed alternately to two approximately 90-day periods of long [16 h of light, 8 h of darkness (16L:8D)] and short (10L:14D) days and then to 10L:14D for an additional 165 days. Blood samples were collected twice weekly to monitor plasma profiles of progesterone, PRL, and total T4, and during the second 16L:8D photoperiod, hourly for one 24-h period to assess melatonin release. Lesions increased (P < 0.001) the interval between the start of long days and cessation of estrous cycles during both long day periods, but did not affect the interval between the start of short days and the onset of estrous cycles for either the first (P = 0.08) or second (P > 0.10) short day period. Consequently, the durations of both anestrous periods were shorter (P < 0.001) for AHAX than for sham ewes. AHA lesions did not affect (P > 0.10) diurnal patterns of melatonin release. No effects (P > 0.10) of lesions were evident on plasma patterns of PRL or total T4 for any short or long day photoperiod. Development of photorefractoriness to constant short days either did not occur or was markedly delayed in five of nine AHAX (P < 0.01) ewes, whereas the other four AHAX ewes became refractory at a time similar (P > 0.10) to that in sham ewes. Responses to inhibitory long day photoperiods and constant short days were highly (P < 0.05) correlated (r = 0.74) and appeared dependent upon the extent of the AHA lesion. These results suggest that AHA lesions disrupt neuronal pathways mediating the effects of shifts in photoperiod on reproductive activity and development of photorefractoriness to constant short days. Our results suggest that the effects of AHA lesions are confined to the termination of reproductive activity, and that different neural pathways participate in photostimulation vs. photosuppression or photorefractoriness.

Effect of anterior hypothalamic area lesions on photoperiod-induced shifts in reproductive activity of the ewe.

The areas of the brain involved in photoperiodic control of reproduction are not well defined. The objective of this study was to determine whether anterior hypothalamic area (AHA) lesions in the ewe affected the responses of the reproductive system to shifts in the length of the daily photoperiod and development of photorefractoriness to a constant short day photoperiod. Eleven intact ewes received bilateral radiofrequency lesions of the AHA (AHAX), and five received sham lesions (sham). The ewes then were placed in photochambers and exposed alternately to two approximately 90-day periods of long [16 h of light, 8 h of darkness (16L:8D)] and short (10L:14D) days and then to 10L:14D for an additional 165 days. Blood samples were collected twice weekly to monitor plasma profiles of progesterone, PRL, and total T4, and during the second 16L:8D photoperiod, hourly for one 24-h period to assess melatonin release. Lesions increased (P < 0.001) the interval between the start of long days and cessation of estrous cycles during both long day periods, but did not affect the interval between the start of short days and the onset of estrous cycles for either the first (P = 0.08) or second (P > 0.10) short day period. Consequently, the durations of both anestrous periods were shorter (P < 0.001) for AHAX than for sham ewes. AHA lesions did not affect (P > 0.10) diurnal patterns of melatonin release. No effects (P > 0.10) of lesions were evident on plasma patterns of PRL or total T4 for any short or long day photoperiod. Development of photorefractoriness to constant short days either did not occur or was markedly delayed in five of nine AHAX (P < 0.01) ewes, whereas the other four AHAX ewes became refractory at a time similar (P > 0.10) to that in sham ewes. Responses to inhibitory long day photoperiods and constant short days were highly (P < 0.05) correlated (r = 0.74) and appeared dependent upon the extent of the AHA lesion. These results suggest that AHA lesions disrupt neuronal pathways mediating the effects of shifts in photoperiod on reproductive activity and development of photorefractoriness to constant short days. Our results suggest that the effects of AHA lesions are confined to the termination of reproductive activity, and that different neural pathways participate in photostimulation vs. photosuppression or photorefractoriness.

Hypothermia in Acute Lymphoblastic Leukemia

Hypothermia in Acute Lymphoblastic Leukemia

Respiratory responses to combined hypoxia and hypothermia in rats after posterior hypothalamic lesions

Urethane-anaesthetised rats were exposed to hypoxia (7% O2 in N2) for 5 min periods while body core temperature (Tbc) was maintained within the normal range (37-38 degrees C) using an abdominal heat exchanger. Animals were exposed to hypoxia and after placement of electrolytic lesions in either the anterior (n = 6) or posterior hypothalamus (n = 6). Neither lesion altered respiration while rats breathed air at either Tbc. At normal Tbc, rats responded to hypoxia with increased ventilation throughout the exposure period. This response was unchanged by lesions in either location. At reduced Tbc rats responded to hypoxia with an initial increase in ventilation followed by depression to below air-breathing levels. This depressive response was unchanged after anterior hypothalamic lesions but eliminated after posterior hypothalamic lesions. It is concluded that neurons either originating in the posterior hypothalamus, or passing through it, play a role in the interaction between cold and hypoxia which leads to inhibition of respiration.

Immunological analysis of the rats with anterior hypothalamic lesions

We have previously identified the suppression of lymphocyte blastogenesis and the acceleration of growth of subcutaneous tumors by bilateral anterior hypothalamic lesions in rats. The present study was performed to clarify the changes in lymphocyte subsets and natural killer (NK) activity after making the lesions. The influence on immunological memory was also studied. The CD4/CD8 ratio of peripheral blood lymphocytes and spleen cells, T cell receptor αβ-positive cells of the thymocytes and NK activity of the spleen cells decreased significantly. Major histocompatibility complex (MHC) antigen expression on RBL-1 cells injected intraperitoneally into pre-immunized rats was also suppressed. These results suggest that the anterior hypothalamus has some influences on the control of the cellular immunological functions at the peripheral level, on the maturation of T cells at the level of thymus and on the antigen recognition by T cell receptors and MHC antigens.

Transforming growth factor alpha contributes to the mechanism by which hypothalamic injury induces precocious puberty.

It has long been known that lesions of the hypothalamus lead to female sexual precocity. While an increased production of luteinizing hormone-releasing hormone (LHRH), the neurohormone that controls sexual development, appears to mediate the advancement of puberty induced by these lesions, little is known about the mechanism(s) by which hypothalamic injury activates LHRH secretion. Since brain lesions result in accumulation of neurotrophic/mitogenic activities in the injured area, we tested the hypothesis that transforming growth factor alpha (TGF-alpha), a mitogenic polypeptide recently shown to stimulate LHRH release, is produced in response to hypothalamic injury and mediates the effect of the lesion on puberty. Radiofrequency lesions of the preoptic area-anterior hypothalamic area (POA-AHA) of 22-day-old female rats resulted in precocious puberty within 7 days after the operation. RNA blot hybridization revealed that lesion-induced puberty was preceded by an increase in TGF-alpha mRNA levels in the POA-AHA. Epidermal growth factor (EGF) mRNA was undetectable in both intact and lesioned hypothalami. TGF-alpha mRNA levels, quantitated by RNase protection assays, were 3.5-fold greater in lesioned animals approaching puberty than in age-matched controls. Immunohistochemical studies, utilizing single- and double-staining procedures, demonstrated the presence of TGF-alpha precursor-like immunoreactivity in reactive astrocytes surrounding the lesion site. Hybridization histochemistry showed increased TGF-alpha mRNA expression in cells of the same area, further implicating reactive astrocytes as a site of TGF-alpha synthesis. The actions of TGF-alpha are mediated by its interaction with EGF receptors. Continuous infusion of RG-50864, an inhibitor of EGF receptor kinase activity, at the site of injury prevented the advancement of puberty induced by the lesion. These results suggest that TGF-alpha acting via EGF-like receptors contributes to the acceleration of puberty induced by anterior hypothalamic lesions. They also indicate that activation of TGF-alpha gene expression in glial cells is a component of the hypothalamic response to injury.

Lesions of the anterior hypothalamic area increase arterial pressure in NaCl-sensitive spontaneously hypertensive rats

In NaCl-sensitive spontaneously hypertensive rats, diets high in NaCl increase arterial pressure and peripheral sympathetic nervous system activity and decrease the sympatho-inhibition mediated by the anterior hypothalamic area. To test the importance of the defect in anterior hypothalamic area-mediated sympatho-inhibition in the pathogenesis of NaCl-sensitive hypertension, bilateral ibotenic acid lesions of the anterior hypothalamic area were made in NaCl-sensitive spontaneous hypertensive rats, in NaCl-resistant spontaneously hypertensive rats and in normotensive, NaCl-resistant Wistar Kyoto rats. In NaCl-sensitive spontaneous hypertensive rats on a basal NaCl diet, the anterior hypothalamic area lesions caused a rapid rise in arterial pressure within the first week after surgery; by 21 days after surgery, mean systolic arterial pressure of the lesion group was 24 mmHg higher than that of the sham-operated group. In a second experiment, NaCl-sensitive spontaneous hypertensive rats were placed on an 8% NaCl diet 1 day after the lesion of the anterior hypothalamic area. 5 days after the operation, the lesion group of NaCl-sensitive spontaneous hypertensive rats on the 8% NaCl diet had a significantly higher arterial pressure than the sham-operated group, but by 1 week after the lesion, arterial pressures were not significantly different between the lesion and sham-operated NaCl-sensitive spontaneous hypertensive rats on the high NaCl diet. In Wistar Kyoto rats on a basal NaCl diet, lesions of the anterior hypothalamic area resulted in a small, transient elevation of arterial pressure, but no sustained effect. In NaCl-resistant spontaneous hypertensive rats, the anterior hypothalamic area lesions did not affect arterial pressure. These results support the hypothesis that in NaCl-sensitive spontaneous hypertensive rats the anterior hypothalamic area contributes importantly to arterial pressure regulation and the data suggest that both the lesion of the anterior hypothalamic area and the high-NaCl diet may affect arterial pressure regulation through the same mechanism.

MAGNETIC BRAIN STIMULA AND IMMUNE RESPONSE IN THE RAT WITH LESIONED BRAIN STRUCTURES

Rats with electrolytic anterior hypothalamic lesions showed a suppressed Arthus reaction, delayed skin hypersensitivity, and antibody production at 7, 14 and 21 days after immunization with bovine serum albumin (BSA) in complete Freud's adjuvant (CFA). However, magnetic treatment of the brain of rats with anterior hypothalamic or caudate nucleus lesions increased both humoral and cellular sensitivity reactions. These data indicate that magnetic stimulation of the brain is capable of modulating immune functions.

Endotoxin-induced reduction of β-adrenergic binding sites on splenic lymphocytes [formula omitted] and [formula omitted]: Its modulation by anterior hypothalamic lesions

Bacterial endotoxin induced a 38% decrease in the number of β-adrenergic binding sites (Bmax) on splenic lymphocytes, four days after intraperitoneal administration to guinea pigs. No change in the affinity (Kd) for [125-I]-cyanopindolol ([125-I]-CYP) binding was observed. Incubation of guinea pig splenocytes in vitro with different concentrations of bacterial endotoxin for 24 hours resulted in an increased incorporation of [ 3H]-thymidine, a parameter for lymphocyte activation. Activation of splenic lymphocytes with the optimal endotoxin concentration of 100 μg/ml for 24 hours induced a 27% decrease in the Bmax whereas the Kd for [125-I]-CYP binding was not changed. Based on these findings, we speculate that activation of lymphocytes with endotoxin in vitro and in vivo is associated with a reduction in the number of β-adrenergic binding sites on these cells. Anterior hypothalamic (AHA) lesions protected against the endotoxin-induced reduction in the number of β-adrenergic binding sites on lymphocytes. The protective effect of these lesions could not be related to alterations in the plasma levels of cortisol, triiodothyronine (T3), thyroxine (T4), adrenaline and noradrenaline or to splenic noradrenaline content. Since AHA lesions have been shown to inhibit several lymphocyte functions, it is suggested that these lesions prevent lymphocyte activation after in vivo endotoxin administration and through this abrogate the reduction of the β-adrenergic binding sites.

Modification of guinea pig lung anaphylaxis by central nervous system (CNS) perturbations

Since several studies indicate that protection from lethal anaphylaxis is mediated by anterior hypothalamic (AH) lesions, we investigated the hypothesis that central nervous system perturbations can modify release of mediators from antigen-challenged sensitized lungs. Three types of perturbations were made in guinea pigs: AH perturbation (electrodes inserted and the current was applied), anterior hypothalamic sham (AS) (electrodes placed as in the AH group but no current was passed), and posterior hypothalamic (PH) perturbation (electrodes placed and the current was applied). A control group was sham operated (electrodes not inserted). Eleven days after the operation, guinea pigs receiving brain perturbations and half the control group were sensitized to the antigen ovalbumin. The other half of the control group received vehicle only (nonsensitized). Twenty-five days after this procedure, lungs were perfused in situ, and the outflows were collected before and after injection of antigen. The perfusates were assayed for immunoreactive prostaglandin and histamine, and the lungs were assayed for cAMP, guanosine monophosphate, and histamine. Release of mediators and changes in lung cyclic nucleotides after perfusion with antigen were significantly greater in all the antigen-sensitized compared to the nonsensitized animals. Within the anaphylactic groups, significant reductions in mediators and in cyclic nucleotides were found in the animals with perturbations of the AH region compared to the CO animals. The time course of mediator release was not altered. The results extend to the biochemical level, the observation that the perturbation of the AH region can markedly modify the anaphylactic response, and indicate that this effect may be due to altered release of mediators.

Effects of anterior hypothalamic lesions and sham-operations on bacterial endotoxin-induced non-specific airway hyperreactivity in vivo and in vitro.

1. In the present study the effects of anterior hypothalamic (AHA) lesions and sham-operations were investigated on the endotoxin-induced airway hyperreactivity in guinea-pigs. Unoperated, sham-operated and AHA-lesioned guinea-pigs were injected intraperitoneally with Escherichia coli endotoxin and the airway reactivity tested four days later in isolated tracheal spirals and in spontaneously breathing anaesthetized animals. Control animals were given sterile saline. 2. Sham-operated control animals demonstrated a diminished responsiveness of the tracheal spirals in vitro and of the lung resistance (delta R1) in vivo to histamine receptor and cholinoceptor-muscarinic agonists as compared to unoperated control animals. 3. AHA-lesioned control animals showed a responsiveness of the respiratory airways in vitro and in vivo between the values of unoperated and sham-operated control animals, suggesting that lesions partially restored the diminished responsiveness. 4. In unoperated and sham-operated guinea-pigs, endotoxin administration induced hyperreactivity of the tracheal spirals and delta R1 to histamine receptor and cholinoceptor-muscarinic agonists with respect to the control groups. 5. In AHA-lesioned animals, the endotoxin-induced airway hyperreactivity in vitro and in vivo to histamine receptor and cholinoceptor-muscarinic agonists was absent.